BACKGROUND: Debate regarding the alterations of the cardiac innervation in an evolving myocardial infarction and transplanted hearts is still raging and most studies are based on radionuclide uptake of neurotransmitters or on the evaluation of the cardiorespiratory reflex. METHODS: The present investigation, upon human autoptic specimens of 57 infarcts and 8 cardiac transplants, was carried out with traditional neuropathology and modern molecular biology techniques. The specimens were selected for the identification of neurons, nerve fibers and their sheaths. RESULTS: First of all, these techniques confirmed the gross difference in the vulnerability of infarcted myocytes if compared with the local innervation, the metabolism of which is infinitely less oxygen-dependent than that of working myocardium (approximate quantitation below). Delicate technicalities of the traditional silver impregnation for nerves usually yield a large incidence of artifacts. Thereby, only perfect results (20% of cases), corroborated by parallel nerve sheath immunostaining (70% of cases), were retained and documented herein. In the meantime, acidosis and free radicals increase, while catabolite accumulation supervenes. These three factors threaten myocardial viability. Thereby, nervelets can be seen to survive the hyperacute phase of ischemia, but may be in part damaged by the successive granulocytic-macrophage inflammation enzyme lysis of the infarcted muscle. The delayed and incomplete anatomical neural damage is confirmed by the observation of preserved nerve sheaths and neural filaments surviving in postinfarction scars, almost devoid of myocardiocytes. CONCLUSIONS: The rich sympatho-vagal cardiac network might further provide alternative bypasses for post-infarct reinnervation. The functional implications of this process remain unclear.